Aspergillus is a fungus that can commonly infect immunocompromised patients such as those with cancer, HIV/AIDS, solid organ transplants or bone marrow transplants. It is responsible for significant disease and mortality in these patients and thus requires rapid recognition and proper treatment. Unfortunately, current methods for diagnosis of invasive Aspergillus infection either do not perform well or require significant invasive procedures such as a lung biopsy. Therefore, new approaches are needed for the rapid recognition of this infection in susceptible patients. We propose to use the recent advances in analytical chemistry and instrumentation that enable the sensitive detection of volatiles to detect Aspergillus from a breath sample. Initial studies have illustrated that certain volatile compounds are given off by Aspergillus and these can potentially be used to establish the diagnosis. This project proposes to identify and validate biomarkers by studying Aspergillus grown in culture, in an infected animal model and in particularly susceptible patients using a novel and portable sensor called the differential mobility spectrometer (DMS). If successful, we would envision a rapid, simple and non-invasive diagnostic that would enable early and specific diagnosis of invasive Aspergillus infection. This would enable more rapid treatment and should improve patient outcomes. Invasive Aspergillus and other fungal diseases contribute to significant morbidity and mortality in immune-compromised patients. In order to address the need for rapid and non- invasive diagnosis we propose to identify volatile compounds associated with Aspergillus infection and validate their detection in a clinical study using a novel and portable gas sensor, the differential mobility spectrometer. Development of this methodology will ultimately allow better surveillance and targeting of antifungal therapy and improved patient outcomes.